A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology. 

Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine

Abstract Lung cancer is a prevalent cancer type worldwide that often remains asymptomatic in its early stages and is frequently diagnosed at an advanced stage with a poor prognosis due to the lack of effective diagnostic techniques and molecular biomarkers. However, emerging evidence suggests that extracellular vesicles (EVs) may promote lung cancer cell proliferation and metastasis, and modulate the anti-tumor immune response in lung cancer carcinogenesis, making them potential biomarkers for early cancer detection. To investigate the potential of urinary EVs for non-invasive detection and screening of patients at early stages, we studied metabolomic signatures of lung cancer. Specifically, we conducted metabolomic analysis of 102 EV samples and identified metabolome profiles of urinary EVs, including organic acids and derivatives, lipids and lipid-like molecules, organheterocyclic compounds, and benzenoids. Using machine learning with a random forest model, we screened for potential markers of lung cancer and identified a marker panel consisting of Kanzonol Z, Xanthosine, Nervonyl carnitine, and 3,4-Dihydroxybenzaldehyde, which exhibited a diagnostic potency of 96% for the testing cohort (AUC value). Importantly, this marker panel also demonstrated effective prediction for the validation set, with an AUC value of 84%, indicating the reliability of the marker screening process. Our findings suggest that the metabolomic analysis of urinary EVs provides a promising source of non-invasive markers for lung cancer diagnostics. We believe that the EV metabolic signatures could be used to develop clinical applications for the early detection and screening of lung cancer, potentially improving patient outcomes. 

/pdf/metabolomic-investigation-of-urinary-extracellular-vesicles-196od358.pdf

Metabolomic investigation of urinary extracellular vesicles for early detection and screening of lung cancer

Exosome membrane-coated nanosystems: Exploring biomedical applications in cancer diagnosis and therapy

Bleomycin (BLM) is a chemotherapeutic agent with potent antitumor activity against the tumor. However, lung fibrosis is the main drawback that limits BLM use. Tumor targeted, safe, efficient and natural delivery of BLM is important to increase the effectiveness and reduce the toxic side effects. Although tumor derived Exosomes (Exo), provide a potential vehicle for in vivo drug delivery due to their cell tropism. This study primarily focuses on generating a natural delivery platform for Exo loaded with BLM and testing its therapeutic efficacy against cancer.Exosomes were isolated from cancer cells and incubated with BLM. Exo were characterized by transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. We performed in vitro and in vivo analyses to evaluate the effect of Exo-BLM.Exosomes loaded with BLM are highly cancer targeting and cause the cytotoxicity of tumor cells by ROS. The fluorescence images showed that Exo-BLM accumulated in cancer cells. The results revealed that Exo-BLM induces tumor cell apoptosis by the caspase pathway. In vivo, the treatment of Exo-BLM showed targeted ability and enhanced the antitumor activity.This study provides an avenue for specific BLM therapeutics with minimal side effects. 

Bleomycin loaded exosomes enhanced antitumor therapeutic efficacy and reduced toxicity.

Additional file 1 of Metabolomic investigation of urinary extracellular vesicles for early detection and screening of lung cancer

A common approach in the development of therapeutic proteins is the use of synthetic ligands with multivalency, allowing for sophisticated control of signal transduction. Leveraging the emerging concept of liquid-liquid phase separation (LLPS) and its ability to organize cell surface receptors into functional compartments, we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways, thus inducing the rapid, potent, and specific apoptosis of tumor cells. Despite their simplicity, these “triggers”, named phase-separated Tumor Killers (hereafter referred to as psTK), are sufficient to yield interreceptor clustering of death receptors (represented by DR5) and tumor-associated receptors, with the following features: LLPS-mediated robust high-order organization, well-choreographed conditional activation, and broad-spectrum capacity for potently inducing apoptosis of tumor cells. The development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal transduction. This approach enables the branching of cell fate and holds promising potential for targeted therapies against challenging tumors. One-Sentence Summary Engineered modular ligands with phase-separation modalities can drive lethal dialog with tumor cells.

A Phase Separation-Fortified Bi-Specific Adaptor for Conditional Tumor Killing

Abstract Multidrug-resistant Acinetobacter baumannii (MDR-AB) infections are becoming increasingly common. The Real-Time Nosocomial Infection (NI) Surveillance System (RT-NISS) was used to monitor MDR-AB NI in intensive care units (ICUs) to prevent NI outbreaks. Therefore, the RT-NISS was used in the current study to monitor MDR-AB infections in a neurosurgery ICU. Clinical interventions, including recommended antibiotics, bacterial distribution in the patient analysis, and bed adjustments, were carried out based on the monitoring results. The RT-NISS was also used to monitor clinical data, implement, and provide training on NI control. The RT-NISS detected a potential cluster of XDR-AB when five patients admitted to the neurosurgery ICU were tested positive for AB between 11 and 17 June 2019. Only two infected cases originated in the hospital, and there was no NI outbreak. The hospital Infection Control Department took appropriate measures to prevent cross-infection; specifically, an epidemiologic investigation and environmental assessment were conducted, and NI prevention and outbreak management training was provided. In summary, the RT-NISS enhanced the timeliness and efficacy of NI control and surveillance in a neurosurgery ICU. In order to prevent NI outbreaks, the Real-Time Nosocomial Infection (NI) Surveillance System (RT-NISS) was employed to monitor MDR-AB NI in critical care units (ICU). Based on the monitoring data, clinical actions such as required antibiotics, bacterial distribution in the patient analysis, and bed changes were carried out. In a neurosurgery ICU, the RT-NISS improved the timeliness and efficacy of NI control and surveillance.

/pdf/monitoring-multidrug-resistant-acinetobacter-baumannii-1kx8isba.pdf

Monitoring Multidrug-Resistant Acinetobacter Baumannii Infections in The Neurosurgery ICU Using a Real-Time Surveillance System

Recently, biomimetic nanoparticles for tumor−targeted therapy have attracted intensifying interest. Although exosomes are an excellent biomimetic material, numerous challenges are still hindering its clinical applications, such as low yield, insufficient targeting efficiency, and high cost. In this work, urinary exosomes (UEs) with high expression of CD9 and CD47 were extracted from breast cancer patients by a non−invasive method. Here, a nanotechnology approach is reported for tumor homologous targeting via CD9 and phagocytosis escape via CD47 through UE−coated poly (2−ethyl−2−oxazoline)−poly (D, L−lactide) (PEOz−PLA) nanoparticles (UEPP NPs). The cytotoxic agent doxorubicin (DOX)−loaded UEPP (UEPP−D) NPs with an initial particle size of 61.5 nm showed a burst release under acidic condition mimicking the tumor microenvironment. In vitro experiments revealed that UEPP−D NPs exhibited significantly improved cellular uptake, cytotoxicity, and apoptosis in MCF−7 cell lines as compared to DOX−loaded PEOz−PLA nanoparticles (PP−D NPs) and free DOX. More importantly, anti−phagocytosis and pharmacokinetic studies confirmed that UEPP−D NPs had superior immune escape ability and significantly prolonged the drug’s bloodstream circulation in vivo. Finally, UEPP−D NPs showed a markedly higher antitumor efficacy and lower side−toxicity in MCF−7 tumor bearing nude mice model. Thus, this versatile nano−system with immune escape, homologous targeting, and rapid response release characteristics could be a promising tool for breast cancer treatment.

https://www.mdpi.com/2306-5354/9/8/363/pdf?version=1659525213

Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer

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A Phase Separation-Fortified Bi-Specific Adaptor for Conditional Tumor Killing

Monitoring Multidrug-Resistant Acinetobacter Baumannii Infections in The Neurosurgery ICU Using a Real-Time Surveillance System

Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer